State of the Art in Gene Therapy

  • H. J. Haisma
  • M. G. Rots
Conference paper
Part of the Developments in Hematology and Immunology book series (DIHI, volume 38)

Abstract

The elucidation of the complete human genome with approximately 30.000 different genes will lead to new possibilities for diagnosis and prevention of a wide variety of diseases. In addition, this knowledge may be used for the design of new therapeutics, based on the DNA sequence information. One of these approaches is gene therapy, where new genes are introduced in a patient to correct a specific disease. For many years, gene transfer techniques have been used in the laboratory setting to introduce altered or foreign genes into cells in order to produce a specific, desired outcome. Since the 1990s, gene therapy has been studied as a possible means of modifying the genetic makeup of patients to treat a specific disease.

Keywords

Cystic Fibrosis Gene Therapy Adenoviral Vector Critical Limb Ischemia Diphtheria Toxin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Blaese RM, Culver KW, Miller AD, et al. T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years. Science 1995;270: 475–80.PubMedCrossRefGoogle Scholar
  2. 2.
    Aiuti A, Slavin S, Aker M, et al. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 2002;296: 2410–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Cavazzana-Calvo M, Hacein-Bey S, de Saint BG, et al. Gene therapy of human severe combined immunodeficiency (SCID)-Xl disease. Science 2000;288:669–72.PubMedCrossRefGoogle Scholar
  4. 4.
    Kay MA, Manno CS, Ragni MV, et al. Evidence for gene transfer and expression of factor VIII in patients with severe hemophilia A. N Engl J Med 2001;344:1735–42.CrossRefGoogle Scholar
  5. 5.
    Roth DA, Tawa NE Jr, O’Brien JM, Treco DA, Seiden RF. Nonviral transfer of the gene encoding coagulation factor IX in haemophilia B patients treated with an AAV vector. Nat. Genet 2000;24:257–61.CrossRefGoogle Scholar
  6. 6.
    Crystal RG, McElvaney NG, Rosenfeld MA, et al. Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nat\Genet 1994;8:42–51.PubMedGoogle Scholar
  7. 7.
    Harvey BG, Leopold PL, Hackett NR, et al. Airway epithelial CFTR mRNA expression in cystic fibrosis patients after repetitive administration of a recombinant adenovirus. J Clin Invest 1999; 104:1245–55.PubMedCrossRefGoogle Scholar
  8. 8.
    Tio RA, Tkebuchava T, Scheuermann TH, et al. Intramyocardial gene therapy with naked DNA encoding vascular endothelial growth factor improves collateral flow to ischemic myocardium. Hum Gene Ther 1999; 10: 2953–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Losordo DW, Vale PR, Hendel RC, et al. Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia. Circulation 2002;105:2012–18.PubMedCrossRefGoogle Scholar
  10. 10.
    Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998;97: 1114–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Isner JM, Pieczek A, Schainfeld R, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 1996;348:370–74.PubMedCrossRefGoogle Scholar
  12. 12.
    Rainov NG. A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther 2000; 11: 2389–401.PubMedCrossRefGoogle Scholar
  13. 13.
    Abonour R, Williams DA, Einhorn L, et al. Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells. Nat Med 2000;6:652–58.PubMedCrossRefGoogle Scholar
  14. 14.
    Swisher SG, Roth JA, Nemunaitis J, et al. Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer. J Natl Cancer Inst 1999;91: 763–71.PubMedCrossRefGoogle Scholar
  15. 15.
    Dummer R, Bergh J, Karlsson Y, et al. Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors. Cancer Gene Ther 2000;7:1069–76.PubMedCrossRefGoogle Scholar
  16. 16.
    Khuri FR, Nemunaitis J, Ganly I, et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cis-platin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 2000;6:879–85.PubMedCrossRefGoogle Scholar
  17. 17.
    Ponder KP, Melniczek JR, Xu L, et al. From the Cover: Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogs. Proc Natl Acad Sci USA 2002;99:13102–07.PubMedCrossRefGoogle Scholar
  18. 18.
    Ikawa M, Tergaonkar V, Ogura A, Ogonuki N, Inoue K, Verma IM. Restoration of spermatogenesis by lentiviral gene transfer: offspring from infertile mice. Proc Natl Acad Sci USA 2002;99:7524–29.PubMedCrossRefGoogle Scholar
  19. 19.
    Pawliuk R, Westerman KA, Fabry ME, et al. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science 2001;294: 2368–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Acland GM, Aguirre GD, Ray J, et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 2001;28:92–95.PubMedGoogle Scholar
  21. 21.
    DelloRusso C, Scott JM, Hartigan-O’Connor D, et al. Functional correction of adult mdx mouse muscle using gutted adenoviral vectors expressing full-length dystrophin. Proc Natl Acad Sci USA 2002;99:12979–84.PubMedCrossRefGoogle Scholar
  22. 22.
    Muramatsu S, Fujimoto K, Ikeguchi K, et al. Behavioral recovery in a primate model of Parkinson’s disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes. Hum Gene Ther 2002;13:345–54.PubMedCrossRefGoogle Scholar
  23. 23.
    Lee HC, Kim SJ, Kim KS, Shin HC, Yoon JW. Remission in models of type 1 diabetes by gene therapy using a single- chain insulin analogue. Nature 2000;408:483–88.PubMedCrossRefGoogle Scholar
  24. 24.
    Sullivan NJ, Sanchez A, Rollin PE, Yang ZY, Nabel GJ. Development of a preventive vaccine for Ebola virus infection in primates. Nature 2000;408: 605–09.PubMedCrossRefGoogle Scholar
  25. 25.
    Shiver JW, Fu TM, Chen L, et al. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 2002;415:331–35.PubMedCrossRefGoogle Scholar
  26. 26.
    Li Y, McCadden J, Ferrer F, et al. Prostate-specific expression of the diphtheria toxin A chain (DT-A): studies of inducibility and specificity of expression of prostate- specific antigen promoter-driven DT-A adenoviral-mediated gene transfer. Cancer Res 2002;62:2576–82.PubMedGoogle Scholar
  27. 27.
    Bohl D, Naffakh N, Heard JM. Long-term control of erythropoietin secretion by doxycycline in mice transplanted with engineered primary myoblasts. Nat Med 1997;3:299–305.PubMedCrossRefGoogle Scholar
  28. 28.
    Trask TW, Trask RP, Aguilar-Cordova E, et al. Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. Mol Ther 2000;1:195–203.PubMedCrossRefGoogle Scholar
  29. 29.
    Herman JR, Adler HL, Aguilar-Cordova E, et al. In situ gene therapy for adenocarcinoma of the prostate: a phase I clinical trial. Hum Gene Ther 1999;10:1239–49.PubMedCrossRefGoogle Scholar
  30. 30.
    Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 1997; 275:1320–23.PubMedCrossRefGoogle Scholar
  31. 31.
    Wickham TJ, Mathias P, Cheresh DA, Nemerow GR. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 1993;73:309–19.PubMedCrossRefGoogle Scholar
  32. 32.
    Haisma HJ, Pinedo HM, Rijswijk A, et al. Tumor-specific gene transfer via an adenoviral vector targeted to the pan-carcinoma antigen EpCAM. Gene Ther 1999;6:1469–74.PubMedCrossRefGoogle Scholar
  33. 33.
    Heideman DA, Snijders PJ, Craanen ME, et al. Selective gene delivery toward gastric and esophageal adenocarcinoma cells via EpCAM-targeted adenoviral vectors. Cancer Gene Ther 2001;8:342–51.PubMedCrossRefGoogle Scholar
  34. 34.
    Haisma HJ, Grill J, Curiel DT, et al. Targeting of adenoviral vectors through a bispecific single-chain antibody. Cancer Gene Ther 2000;7:901–04.PubMedCrossRefGoogle Scholar
  35. 35.
    Dirven CM, Grill J, Lamfers ML, et al. Gene therapy for meningioma: improved gene delivery with targeted adenoviruses. J Neurosurg 2002;97: 441–49.PubMedCrossRefGoogle Scholar
  36. 36.
    Witlox MA, van Beusechem VW, Grill J, et al. Epidermal growth factor receptor targeting enhances adenoviral vector based suicide gene therapy of osteosarcoma. J Gene Med 2002;4: 510–16.PubMedCrossRefGoogle Scholar
  37. 37.
    van der Poel HG, Molenaar B, van Beusechem VW, et al. Epidermal growth factor receptor targeting of replication competent adenovirus enhances cytotoxicity in bladder cancer. J Urol 2002;168:266–72.PubMedCrossRefGoogle Scholar
  38. 38.
    Grill J, van Beusechem VW, Van D, et al. Combined targeting of adenoviruses to integrins and epidermal growth factor receptors increases gene transfer into primary glioma cells and spheroids. Clin Cancer Res 2001; 7:641–50.PubMedGoogle Scholar
  39. 39.
    Krasnykh V, Dmitriev I, Mikheeva G, Miller CR, Belousova N, Curiel DT. Characterization of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob. J Virol 1998;72:1844–52.PubMedGoogle Scholar
  40. 40.
    Roelvink PW, Mi LG, Einfeld DA, Kovesdi I, Wickham TJ. Identification of a conserved receptor-binding site on the fiber proteins of CAR-recognizing adenoviridae. Science 1999;286: 1568–71.PubMedCrossRefGoogle Scholar
  41. 41.
    van Beusechem VW, van Rijswijk AL, van Es HH, Haisma HJ, Pinedo HM, Gerritsen WR. Recombinant adenovirus vectors with knobless fibers for targeted gene transfer. Gene Ther 2000;7:1940–46.PubMedCrossRefGoogle Scholar
  42. 42.
    Haviv YS, Curiel DT. Conditional gene targeting for cancer gene therapy. Adv Drug Deliv Rev 2001;53:135–54.PubMedCrossRefGoogle Scholar
  43. 43.
    Adachi Y, Reynolds PN, Yamamoto M, et al. A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. Cancer Res 2001 ;61:7882–88.PubMedGoogle Scholar
  44. 44.
    Yamamoto M, Alemany R, Adachi Y, Grizzle WE, Curiel DT. Characterization of the cyclooxygenase-2 promoter in an adenoviral vector and its application for the mitigation of toxicity in suicide gene therapy of gastrointestinal cancers. Mol Ther 2001;3:385–94.PubMedCrossRefGoogle Scholar
  45. 45.
    Siders WM, Halloran PJ, Fenton RG. Melanoma-specific cytotoxicity induced by a tyrosinase promoter- enhancer/herpes simplex virus thymidine kinase adenovirus. Cancer Gene Ther 1998;5:281–91.PubMedGoogle Scholar
  46. 46.
    Rots MG, Dmitriev I, Kashentseva E, Curiel DT. A tyrosinase-controlled replicative adenovirus displays melanoma-specific cell killing. Mol Ther 2001;3:S347 (abstract).Google Scholar
  47. 47.
    McLaughlin PM, Harmsen MC, Dokter WH, et al. The epithelial glycoprotein 2 (EGP-2) promoter-driven epithelial- specific expression of EGP-2 in transgenic mice: a new model to study carcinoma-directed immunotherapy. Cancer Res 2001;61:4105–11.PubMedGoogle Scholar
  48. 48.
    Culver KW, Ram Z, Wallbridge S, Ishii H., Oldfield EH, Blaese RM. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 1992;256: 1550–52.PubMedCrossRefGoogle Scholar
  49. 49.
    Pitts JD. Cancer gene therapy: a bystander effect using the gap junctional pathway. Mol Carcinog 1994;11:127–30.PubMedCrossRefGoogle Scholar
  50. 50.
    Rainov NG. A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther 2000; 11:2389–401.PubMedCrossRefGoogle Scholar
  51. 51.
    Wadia JS, Dowdy SF. Protein transduction technology. Curr Opin Biotechnol 2002;13:52–56.PubMedCrossRefGoogle Scholar
  52. 52.
    Weyel D, Sedlacek HH, Muller R, Brusselbach S. Secreted human beta-glucuronidase: a novel tool for gene-directed enzyme prodrug therapy. Gene Ther 2000;7:224–31.PubMedCrossRefGoogle Scholar
  53. 53.
    de Graaf M, Boven E, Oosterhoff D, et al. A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug. Br J Cancer 2002;86: 811–18.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • H. J. Haisma
  • M. G. Rots
    • 1
  1. 1.Dept of Therapeutic Gene Modulation, University Centre for PharmacyUniversity of GroningenGroningenThe Netherlands

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